Bone fractures attributable to osteoporosis are a significant problem. Vertebral fractures are among the most common;everyone in two women is expected to have at least one vertebral fracture in their lifetime. The gold-standard for quantitative assessment of fracture risk is bone mineral density (BMD). However, prediction of fracture risk from BMD has had limited success. Additional microstructural properties of cancellous bone are known to contribute to the quantitative assessment of vertebral bone quality and prediction of bone strength. However, these are difficult to measure in human spine in vivo. Digital tomosynthesis (DTS) is a technique that allows for imaging of focused planes in objects. The blurring in the image that is caused by other planes of the object which would make quantitative analysis using an x-ray film very difficult is reduced to a great extent in DTS. The successive acquisition of images during a single DTS scan allows for collection of a series of images each of which is focused on a different plane of the object. This provides a digital equivalent of a series of x-ray films that would be obtained from physical slices of the object. Furthermore, DTS has a good in-plane resolution, fast, relatively cheap and exposes the patient to a lower radiation dose than a CT scan. The microstructure/texture parameters of cancellous bone that have been found to have clinical significance and related to important mechanical properties of vertebrae are amenable to analyses that can be performed on DTS images. However, DTS has not been examined for its value in quantitative analysis of bone quality. Therefore, our overall goal is to develop improved markers of vertebral bone fragility and fracture risk based on DTS imaging. In this period, we propose an in vitro study to examine the feasibility of DTS for quantification of vertebral bone microstructure and for predicting vertebral bone failure properties using human cadaveric vertebrae. The specific goals of the proposed period are: 1) Using human cadaver vertebrae, determine the size and plane of regions of interest for DTS analysis that maximize correlation between DTS and microcomputed tomography (?CT) parameters, and calibrate DTS with ?CT. 2) Using human cadaver vertebrae, ?CT, DEXA, HRCT, DTS and mechanical testing, to determine the extent to which DTS-based microstructural variability predicts vertebral strength and brittleness. 3) Using human cadaver vertebrae, ?CT, DEXA, HRCT, DTS and mechanical testing, determine the extent to which DTS-based microstructural variability predicts vertebral creep. PUBLIC HEALTH RELEVANCE: This project is designed to determine whether a new application of a clinically available imaging system, namely digital tomosynthesis, can be used to measure vertebral bone microstructural properties and predict vertebral strength, brittleness and deformation. The results will be used to define parameters that can be more effective in estimating vertebral fracture risk and strategies to restore bone structure. The knowledge gained form this research may substantially change our clinical approach for predicting risk of fracture and treating osteoporosis, a disease with a large impact on the elderly population.